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• W1033253607 abstract "Abstract Toll like receptors (TLR) are a major class of pathogen recognition receptors that trigger potent dendritic cell DC activation and present an important immunotherapeutic target. Combination therapy of established tumors by local injection of CpG oligonucleotides (TLR9 agonists) and blockade of IL-10 signaling results in tumor rejection in mice. Using the MCA38 colon carcinoma and B16 melanoma models, CpG treatment alone drastically reduces tumor growth for the duration of treatment, but does not lead to tumor rejection. Local tumor injection of MCA38 tumors with CpG oligonucleotides and intra-peritoneal anti-IL10R antibody led to rapid production of CCL2, TNF- ƒÑ and IL-6 that were detectable in serum after 2 hours. 24 hours after CpG treatment, IL-10, IL-12, and IFN-ƒx were also detectable in serum. Cytokine production at both 2 hour and 24 hour time-points was partially dependent upon blockade of IL-10 signaling. To examine activation of tumor-infiltrating leukocytes, ex vivo cultures of tumor-isolated cells were set up at time-points following CpG injection. Significant production of TNF- ƒÑ, IL-6 and IL-10 was observed only at 2 hours with blockade of IL-10 signaling. The transient period of cytokine production was matched at the cellular level: Prior to treatment MCA38 tumors comprise of ~40% tumor-infiltrating leukocytes (TIL) which are mostly CD11b+CD11c+ cells characteristic of the macrophage or DC lineage. 24 hours following treatment, TILs were predominantly CD11b+Ly6G+ cells. Our results show that CpG treatment of tumors induces rapid activation of tumor-infiltrating cells that is highly potentiated at early time-points by the blockade of IL-10 signaling." @default.
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• W1033253607 date "2009-04-01" @default.
• W1033253607 modified "2023-09-27" @default.
• W1033253607 title "Tumor IL-10 forms an immediate non-redundant blockade to CpG-induced activation of tumor-infiltrating DC and macrophages (41.61)" @default.
• W1033253607 doi "https://doi.org/10.4049/jimmunol.182.supp.41.61" @default.
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